ArticleCancer research2019
HNF4α-Deficient Fatty Liver Provides a Permissive Environment for Sex-Independent Hepatocellular Carcinoma.
Article in Cancer research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 35 citations in OpenAlex.
- Article
- Targeting the hepatic circadian clock concomitant with tyrosine kinase inhibition reverses late-stage hepatocellular carcinoma.Cell reports · 2025Article
- Poor sleep and hepatic steatosis contribute to poorer quality of life in people with human immunodeficiency virus.World journal of gastroenterology · 2025Observational
- Cell Function Experiments and Bioinformatics Analysis Jointly Revealed the Antineoplastic Effect of Lumican on Hepatocellular Carcinoma.Phenomics (Cham, Switzerland) · 2025Article
- Extracellular Vesicles, Circadian Rhythms, and Cancer: A Comprehensive Review with Emphasis on Hepatocellular Carcinoma.Cancers · 2024Review
- HNF4α in Hepatocyte Health and Disease.Seminars in liver disease · 2023Review
- Lipid droplets are intracellular mechanical stressors that impair hepatocyte function.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Circadian regulator BMAL1::CLOCK promotes cell proliferation in hepatocellular carcinoma by controlling apoptosis and cell cycle.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Obesity, non-alcoholic fatty liver disease and hepatocellular carcinoma: current status and therapeutic targets.Frontiers in endocrinology · 2023Review
- HNF4α isoforms: the fraternal twin master regulators of liver function.Frontiers in endocrinology · 2023Review
- Expression of p-STAT3 and c-Myc correlates with P2-HNF4α expression in nonalcoholic fatty liver disease (NAFLD).Oncotarget · 2022Article
- Hepatic circadian and differentiation factors control liver susceptibility for fatty liver disease and tumorigenesis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Adipose tissue-specific ablation of Ces1d causes metabolic dysregulation in mice.Life science alliance · 2022Article
- Manifold Roles of Ceramide Metabolism in Non-Alcoholic Fatty Liver Disease and Liver Cancer.Advances in experimental medicine and biology · 2022Article
- Antisense RNAs Influence Promoter Usage of Their Counterpart Sense Genes in Cancer.Cancer research · 2021Article
- HNF4A defines tissue-specific circadian rhythms by beaconing BMAL1::CLOCK chromatin binding and shaping the rhythmic chromatin landscape.Nature communications · 2021Article
- Hepatic sexual dimorphism - implications for non-alcoholic fatty liver disease.Nature reviews. Endocrinology · 2021Review
- The Histone Variant MacroH2A1 Impacts Circadian Gene Expression and Cell Phenotype in an In Vitro Model of Hepatocellular Carcinoma.Biomedicines · 2021Article
- The Role of the PRMT5-SND1 Axis in Hepatocellular Carcinoma.Epigenomes · 2021Article
- Epigenetic Mechanisms Involved in HCV-Induced Hepatocellular Carcinoma (HCC).Frontiers in oncology · 2021Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The incidence of hepatocellular carcinoma (HCC) is on the rise worldwide. Although the incidence of HCC in males is considerably higher than in females, the projected rates of HCC incidence are increasing for both sexes. A recently appreciated risk factor for HCC is the growing problem of nonalcoholic fatty liver disease, which is usually associated with obesity and the metabolic syndrome. In this study, we showed that under conditions of fatty liver, female mice were more likely to develop HCC than expected from previous models. Using an inducible knockout model of the tumor-suppressive isoform of hepatocyte nuclear factor 4 alpha ("P1-HNF4α") in the liver in combination with prolonged high fat (HF) diet, we found that HCC developed equally in male and female mice as early as 38 weeks of age. Similar sex-independent HCC occurred in the "STAM" model of mice, in which severe hyperglycemia and HF feeding results in rapid hepatic lipid deposition, fibrosis, and ultimately HCC. In both sexes, reduced P1-HNF4α activity, which also occurs under chronic HF diet feeding, increased hepatic lipid deposition and produced a greatly augmented circadian rhythm in IL6, a factor previously linked with higher HCC incidence in males. Loss of HNF4α combined with HF feeding induced epithelial-mesenchymal transition in an IL6-dependent manner. Collectively, these data provide a mechanism-based working hypothesis that could explain the rising incidence of aggressive HCC. SIGNIFICANCE: This study provides a mechanism for the growing incidence of hepatocellular carcinoma in both men and women, which is linked to nonalcoholic fatty liver disease.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.